Receptors diffusing over the surface of a cell allow it to sense its environment and respond to it. Often the aggregation of these receptors is crucial to both the capture of external ligands, and the turning on or off of cellular responses. The investigators will focus on receptors with two different types of roles in the immune response. 1) Antigens aggregate cell surface immunoglobulin and in the process initiate responses in B cells, basophils, and mast cells. 2) Interleukin 2 (IL-2), induces the aggregation of IL-2 receptors on activated T cells generating signals that lead to the control of T cell growth and IL-2 secretion. Their aim is to understand the underlying physical chemistry of these types of aggregation, to use this understanding to develop mathematical models that can predict the time course of aggregate formation, and to relate aggregation states to specific cellular responses. The role of the mathematical models is to help devise rigorous tests of ideas about the system, aid in analyzing data, determine parameter values, and suggest new experiments. They will use rat basophilic leukemia (RBL) cells sensitized with monoclonal anti-haptan IgE bound to high-affinity Fc R1 as a model system to study general properties of ligand-induced receptor aggregation and to study the signaling events initiated by aggregation of IgE-Fc R1 complexes. The formation of IgE aggregates on RBL cells triggers numerous cellular responses, but not all aggregates trigger all responses. To determine what properties are required of an IgE aggregate to make it an effective initiator of a particular response, they will characterize the binding and aggregation properties of haptens of different lengths, flexibilities and valence so that they can predict how the distribution of hapten-IgE aggregates develops in time. They will then compare these predictions with the responses of the RBL cell (tyrosine phosphorylation, calcium fluxes, receptor immobilization, degranulation) to relate surface aggregates to cellular response. They will also use the RBL cell system to study the initial events (and how to block them) that occur when a large antigen or virion attaches to a cell surface. The formation of high affinity cytokine receptors involves the aggregation of distinct proteins. They will use newly engineered soluble multi-chain IL-2 receptors as tools to study the interactions of IL-2 with its receptors. The soluble receptors will also be studied for their potential therapeutic value. The high affinity IL-2 receptor shares a signaling unit with other cytokine receptors. They will develop mathematical models to better understand the effects of shared signaling units.